Onychomycosis is a fungal infection that affects the toenails (˜80% of cases) and the fingernails (˜20% of cases). The most common causative pathogens of onychomycosis are the dermatophytes Trichophyton rubrum and Trichophyton interdigitale (also known as Trichophyton mentagrophytes). These pathogens represent the cause of roughly 70% and 20% of onychomycosis cases, respectively. Other causative agents include dermatophytes such as Epidermophyton floccosum, Trichophyton violaceum, Microsporum gypseum, Trichophyton tonsurans, Trichophyton soudanense, Trichophyton verrucosum, nondermatophyte fungi such as Neoscytalidium (also known as Scytalidium), Scopulariopsis, Aspergillus, Fusarium, Acremonium, and yeasts such as Candida. The infection may involve any component of the nail unit, including the nail matrix, the nail bed or the nail plate. See Blumberg, M. “Onychomycosis,” http://www.emedicine.com/derm/topic300.htm, accessed Jul. 7, 2008.
Distal lateral subungual onychomycosis is the most common form of infection. In this variant, the infection begins around the edges of the nail and can cause inflammation in these areas while concurrently spreading to the underside of the nail. The result is disfigurement of the nail and potentially some pain, discomfort and transmission of infection to other nails. If left untreated, onychomycosis can result in permanent nail deformity.
Onychomycosis is a very difficult condition to cure. Today, it is commonly treated with an antifungal medication that is delivered to the systemic circulation, in spite of the fact that the onychomycosis infection is localized to the nail structure. This can result in serious and unwanted side effects, including gastrointestinal symptoms, liver abnormalities, rashes, taste disturbances, hypertension, and drug-drug interactions with a wide range of other medications.
Topical drugs for the treatment of onychomycosis are available, but they are not very effective in the treatment of the disease. For example, Penlac® (ciclopirox 8% solution) is a topical treatment which has been approved in the United States for the treatment in immunocompetent patients with mild to moderate onychomycosis of fingernails and toenails without lunula involvement, due to Trichophyton rubrum. However, the drug is not very effective in the treatment of onychomycosis, providing complete cure (defined as clear nail and negative mycology) in less than 10% of the intent-to-treat population in the Phase III studies used to obtain approval in the United States. Further, relapse appears to be a significant issue with this drug. See Casciano J. et al. Manag. Care 2003, 12(3), 47-54; Tosti, A. et al. Dermatology 1998, 197(2), 162-166; Sigurgeirsson, B. et al. Arch. Dermatol. 2002, 138(3), 353-7; and Penlac® prescribing information, http://products.sanofi-aventis.us/penlac/penlac.html, accessed May 19, 2008.
One of the leading anti-fungal agents for oral treatment of onychomycosis is the drug terbinafine. Terbinafine has also been approved by the US Food and Drug Administration in cream, gel, solution and spray dosage forms for use in topical treatment of fungal infections. However, these products are not approved for the treatment of onychomycosis. For example, terbinafine hydrochloride cream 1% (tradename Lamisil®) is available as an over-the-counter product, and the label specifically notes that the product should not be used on nails. (For package information, see http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/020980s0051b1.pdf, accessed Jul. 30, 2010.)
There is a strong need for a new topical drug composition that can provide good efficacy in treating onychomycosis while avoiding the systemic side effects of oral treatments. The present invention satisfies these and other needs.